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European Review For Medical and... Mar 2024The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia.
MATERIALS AND METHODS
A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety.
RESULTS
10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment.
CONCLUSIONS
The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.
Topics: Aged; Humans; Quality of Life; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute; Pathologic Complete Response; Thrombocytopenia
PubMed: 38497866
DOI: 10.26355/eurrev_202403_35597 -
Kardiologia Polska 2024Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and cost-effective inflammatory biomarker, the neutrophil-to-lymphocyte ratio (NLR) may be beneficial in cardiovascular medicine.
AIMS
This meta-analysis examines the diagnostic and prognostic performance of the NLR in ACS.
METHODS
We systematically searched PubMed Central, Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov databases. The search spanned from databases inception to January 10, 2024. The findings were aggregated into normalized mean differences with 95% confidence intervals.
RESULTS
Ninety articles, with 45 990 participants, were included. Pooled analysis of the NLR varied and was higher in ST-segment elevation myocardial infarction (STEMI) vs. non-ST-segment elevation myocardial infarction patients (4.94 ± 3.24 vs. 3.24 ± 2.74), acute myocardial infarction vs. unstable angina (4.47 ± 3.43 vs. 2.97 ± 1.58), ACS vs. stable angina (SA) (5.45 ± 4.28 vs. 2.46 ± 2.15), and ACS vs. controls (5.31 ± 4.01 vs. 2.46 ± 2.45). The NLR also was associated with ACS mortality, with survivors having lower results (3.67 ± 2.72 vs. 5.56 ± 3.93). Subanalysis showed that differences in the NLR were observed in STEMI survivors (4.28 ± 3.24 vs. 6.79 ± 3.98). Of ACS patients with major cardiovascular events (MACE) vs. without MACE, the NLR was 6.29 ± 4.89 vs. 3.82 ± 4.12. In STEMI patients, the NLR differed between those with and without MACE (6.99 ± 5.27 vs. 4.99 ± 4.12).
CONCLUSIONS
The NLR is an effective tool for differentiating between different types of ACS. A high NLR is associated with ACS and increased MACE at 30 days. The NLR also appears to be a good predictor of MACE risk, at least in STEMI patients.
Topics: Humans; Prognosis; Acute Coronary Syndrome; ST Elevation Myocardial Infarction; Neutrophils; Lymphocytes; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention
PubMed: 38493452
DOI: 10.33963/v.phj.99554 -
BMC Women's Health Mar 2024We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD).
METHODS
We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment.
RESULTS
Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I = 97.5%, random-effect model).
CONCLUSION
The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis.
Topics: Humans; Female; Bone Density; Neutrophils; Postmenopause; Osteoporosis; Bone Diseases, Metabolic; Lymphocytes; Osteoporosis, Postmenopausal
PubMed: 38461235
DOI: 10.1186/s12905-024-03006-1 -
Medicine Mar 2024Leukocyte parameters are predicted to be affected in patients with metabolic syndrome (MetS). We conducted a systematic review and meta-analysis to study the association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leukocyte parameters are predicted to be affected in patients with metabolic syndrome (MetS). We conducted a systematic review and meta-analysis to study the association between white blood cell parameters (WBC) in people with and without MetS.
METHODS
PubMed, EMBASE, Scopus and Cochrane Library databases were searched according to the study protocol. The standardized mean difference (SMD) and 95% confidence intervals (CI) of leukocyte markers between individuals with and without MetS were pooled using an inverse variance model. Additionally, a subgroup analysis by sex was performed where possible. Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for Randomized Controlled Trials (RCTs).
RESULTS
Of 6068 articles identified, 63 were eligible for the study. Compared to controls, individuals with MetS showed significantly higher concentrations of total leukocyte count (SMD [95% CI]: 0.60 [0.55-0.65]; P < .00001; I2 = 100%), neutrophil counts (0.32 [0.28-0.37]; P < .00001; I2 = 99%), lymphocyte counts (0.15 [0.07-0.23]; P = .0004; I2 = 100%), basophil counts (0.01 [0.00-0.02]; P = .02; I2 = 98%), monocyte counts (0.05 [0.02-0.09]; P = .003; I2 = 99%), and neutrophil-to-lymphocyte ratio (0.24 [0.15-0.33]; P < .00001; I2 = 98%). There were no significant differences in the eosinophil count (0.02 [-0.01 to 0.05]; P = .19; I2 = 96%) and monocyte-to-lymphocyte ratio (0.06 [-0.05 to 0.17]; P = .27; I2 = 100%) between patients with and without MetS, however, the lymphocyte-to-monocyte ratio (0.52 [-0.81 to -0.23]; P = .0005; I2 = 52%) tended to be significantly lower in patients with MetS.
CONCLUSION
Biomarkers such as total leukocyte count, neutrophil count, lymphocyte count, basophil count, monocyte count and neutrophil-to-lymphocyte ratio are associated with higher levels in patients in MetS and thus can potentially be used for early detection of MetS.
Topics: Humans; Metabolic Syndrome; Leukocytes; Leukocyte Count; Neutrophils; Lymphocytes
PubMed: 38457562
DOI: 10.1097/MD.0000000000037331 -
Experimental & Molecular Medicine Mar 2024Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections,... (Review)
Review
Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Macrophages
PubMed: 38448692
DOI: 10.1038/s12276-024-01182-6 -
Cureus Jan 2024Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute... (Review)
Review
The Potential Role of NOD2/CARD15 Genotype as a Prognostic Indicator for Bone Marrow Transplantation Outcomes in Patients With Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Systematic Review.
Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.
PubMed: 38361685
DOI: 10.7759/cureus.52329 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Bone Apr 2024This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in... (Review)
Review
PURPOSE
This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in relation to fracture healing.
METHODS
A literature search was performed using the PubMed database. The quality of the articles was evaluated using critical appraisal checklists.
RESULTS
Thirty one studies were included in this review. These studies consistently support that neutrophils exert both beneficial and detrimental effects on bone regeneration, influenced by Tumor Necrosis Factor-α (TNF-α), Interleukin 8 (IL-8), mast cells, and macrophages. The N2 phenotype has recently emerged as one promoter of bone healing. The N1 phenotype has progressively been connected with inflammatory neutrophils during fracture healing.
CONCLUSIONS
This review has pinpointed various aspects and mechanisms of neutrophil influence on bone healing. The recognition of N1 and N2 neutrophil phenotypes potentially shed new light on the dynamic shifts taking place within the Fracture Hematoma (FH).
Topics: Humans; Neutrophils; Bone Regeneration; Fracture Healing; Fractures, Bone; Phenotype
PubMed: 38253189
DOI: 10.1016/j.bone.2024.117021 -
Journal of Immunology Research 2024The density of CD169 macrophages has been reported to positively correlate with the number of CD8 T cells, although this remains controversial. To better understand this... (Meta-Analysis)
Meta-Analysis Review
The density of CD169 macrophages has been reported to positively correlate with the number of CD8 T cells, although this remains controversial. To better understand this topic, we conducted a meta-analysis. We searched the PubMed, Medline, and Web of Science databases for studies that were published before May 2022 and performed a meta-analysis of the incidence of low and high CD169 expression in groups based on CD8 expression using the random-effects model. A total of 10 studies were included in the meta-analysis. The incidence of high CD169 expression in lymph nodes was significantly lower than that of low CD169 expression in the low CD8 expression group (odds ratio (OR): 0.76, 95% confidence interval (CI): 0.6, 0.96); however, the incidence of high CD169 expression in lymph nodes was higher than that of low CD169 expression in the high CD8 expression group (OR: 1.50, 95% CI: 1.08, 2.07). We also found that the expression of CD169 in tumors was lower than that in nontumor tissues (standardized mean difference: -5.29, 95% CI: -7.47, -3.11). The overall survival and hazard ratio of patients with high and low CD169 expression was 0.45 (95% CI: 0.37, 0.55). This analysis showed that high CD169 expression was associated with a high CD8 expression, and low CD169 expression was associated with low CD8 expression. The risk of death was 55% lower for patients with high CD169 expression, and high CD169 expression may be associated with favorable survival outcomes in cancer patients. However, the number and heterogeneity of the studies should be taken into consideration when evaluating the analysis. High-quality randomized controlled trials on the association between CD169 and CD8 expression are needed to verify these effects.
Topics: Humans; CD8-Positive T-Lymphocytes; Lymph Nodes; Neoplasms; Databases, Factual; Macrophages
PubMed: 38250298
DOI: 10.1155/2024/8873767 -
Nature Communications Jan 2024The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal...
The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of [Formula: see text] patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care.
Topics: Humans; Genomics; Hematologic Neoplasms; Mutation; Neoplasms; Whole Genome Sequencing
PubMed: 38238294
DOI: 10.1038/s41467-023-44158-2